Clinical Intelligence Analytics - Study Trends

Study Trends

Study Trends dashboard (Figure 4.1) gives us insights into the tends in recruiting country, average registration to enrollment duration and average study duration over the past 2 decades.

Figure 4.1

The data legends are shared between the charts on the first row. Similarly, the legend is same for the 2 charts on the bottom row.
The data is aggregated on a study level and a study is classified as an International (Both US and non-US), US-only and non-US only study based on the countries of patient recruitment. The analysis excludes studies that does not have any recruiting country information which could be for various reasons such as the recruitment might not have started or the study may not have any enrollments yet.
An international study means that it has recruited patients in the US and at least one other country. 
A non-US only study means that the study has recruited the patients in countries other than the US and no patient was enrolled in the US.
For the other 2 charts on the bottom row, the numbers with a minus sign are positive numbers but are shown as negative numbers just for the display purpose as they are on the opposite side. However, this is not intended. The vertical lines are the average lines to show the distance.

The dashboard can provide insights into the following trends:

1. What's the share of studies by recruiting country?
55% of the studies registered in the US have recruited the patients only from countries other than the US. The share of studies that recruited the patients only inside the US is 39%. International studies are just 6%.


2. What is the trend in the study registration by their location of recruitment?
Now that we know something about the share of the studies based on where the patients were recruited, let's take a look at how it has changed over the last 2 decades. The share of international studies has reduced to less than 5% now from 15% in early 2000's. The trend of US-only studies have also declined sharply from lower 90% in early 2000's to 30-35% level now. The trend of non-US studies have increased consistently in past 2 decades from 44% in year 2005 to 66% in 2019.  
Remember that the share of the studies registered in the past years can change based on the studies that are still recruiting or may recruit in future. Hence, the current trend is the snapshot.

3. How has the average time taken study registration to enrollment changed over the last few years?
The chart shows the trend in the time taken from study registration to patient enrollment or study initiation. The chart also compares side-by-side the duration for studies sponsored by industry or non-industry sponsors.
There are many studies that were registered retrospectively, meaning the studies were registered after they were already started (the first patient was already enrolled). Such retrospective studies were excluded from the analysis. Only for the prospective studies, the registration to enrollment duration is calculated in days.  
It appears that it usually took longer, sometimes 1.5-3 times, for non-industry sponsored studies to begin a study after they are submitted. The trend for non-industry sponsored studies is following a parabolic curve. The average registration to enrollment duration for the non-industry sponsored studies is 125 days which is higher than the overall industry average of 107 days. For the most part, the yearly trend is close to the average line except in year 2010 having an average of 145 days, which is also the highest in recent years.
On the other hand, the industry sponsored studies are initiated quickly and the study initiation duration has improved slightly overall. The average for industry sponsored studies is around 80 days which is well below the industry average of 107 days. The average for the last few years has been consistently near the average line.   

4. How has the average study duration changed over the last few years?
The non-industry sponsored studies takes longer to complete as compared to industry sponsored studies. The average study completion duration for non-industry sponsors is close to 3.5 years which is considerably much higher than the overall industry average of 2.6 years. On the other side, the average for industry sponsors is little above 2 years. The good news is that both type of sponsors have made a significant improvement is past 15 years to bring down the average completion duration to lower levels, possibly signalling great improvements in overall operational efficiency in study conduct.
With that positive note, see you till next time. 

Clinical Intelligence Analytics - Study

Study Dashboard

In study dashboard (Figure 3.1), we will look at certain aspects of study at aggregated level as well as at a study level. 

Figure 3.1

The study dashboard will try to answer following questions:

1. What is the average study completion duration for sponsors from Industry and non-Industry?

For all types of studies (All), the sponsors from Industry completed the studies in about 1.9 years. In comparison to that, sponsors from non-industry took almost 3 years to complete the study.

The observational studies (Obs) took longer to complete. The Industry sponsors with an average of 2.3 years performed fairly better than the non-industry sponsors with an average of 3.2 years.

For interventional type of studies (Int), the average study took 1.8 years for Industry sponsor as compared to 2.9 years for non-industry sponsors.

We may further want to look at the study duration by the phase of the study. Phase 3 studies are large scale and complex in nature and hence, it should take longer to complete when compared with phase 1 and phase 2 studies. Let's see what we find. Only interventional studies go through the drug development phases. If you take a look at Avg Study Duration by Phase chart, Phase 2 studies took longest among all the study phases with an average of 3.3 years. Phase 3 studies took an average of 2.9 years to complete where as phase 4 studies took 2.4 years. Early phase 1 studies took longer than the phase 1 studies.

2. What is the share of sponsors from industry and non-industry in interventional or observational studies?

Almost 80% of studies were interventional studies. 56% of 80% which 70% of total interventional studies were sponsored by non-industry sponsors. The industry sponsors have greater share in interventional studies as compared to its share in observational studies.

3. What percentage of studies were completed between 0 to 3 years or between 8 to 10 years?

40% of the studies were completed between 1 to 3 years. Around 29% studies were completed in less than 1 year. 

4. Which studies took the longest to complete?

There are 44 studies (0.02%) that took more than 30 years to complete. The study that took longest was sponsored by Johnson & Johnson to evaluate the efficacy of oral Levofloxacin in the treatment of chronic Bronchitis. This study took 63 years to complete starting in 1931 and completing in 1994 and has enrolled 367 patients. 

5. At study level, how many medical conditions a particular study is conducted?

See the tabular report to view the number of enrollment, medical conditions and the number of study sites and countries of subject recruitment.

6. In how many countries and facilities did a study recruited patients?

See the tabular report.

The dashboard will show the description of the selected study.

Clinical Intelligence Analytics - Trends by Study Attributes

In the last post, we looked at the growth trends of studies registered, initiated, completed and posted results over the period of last 20 years. We looked at yearly trends and then drilled down at quarterly and monthly trends and compared the growth in current year with the previous year.
In this post, we will see the growth trends of registered studies by study attributes like study type, study phase, Drug/Device and DMC flag over the period. I have filtered out the studies where the study attributes were not specified.

Figure 2.4

This dashboard (Figure 2.4) is an extension of growth trends:
1. Study Submission Trend by Study Type-
The chart shows the trend of studies submitted for interventional and observational types.
The share of interventional studies have decreased. In early 2000's, there were around 90-93% interventional studies and 7-10% observational studies. In last few years, the share of observational studies have increased to 21%.

2.  Study Submission Trend by FDA oversight-
The chart shows the trend of studies by the oversight of the FDA, if the study is for FDA regulated drug or a device. 
Until 2008, the share of the studies for FDA regulated devices was less than 10% which has increased to around 25% now.

3. Study Submission Trend by Study Phase-
 Phase 3 studies are important studies since sponsors apply for FDA approval after that. 
Study type NA are the studies that do not have a phase of a study, and I guess it is mainly for the device related studies. These studies share have increased significantly over the period and I think its because the device related studies share have increased as we observed in the previous chart.
There is a slight drop in the share of phase 1 studies. The share of Phase 2 studies in green has decreased from 43% in 2003 to 12% in 2018. Phase 3 studies have also followed the same trend with the share reducing to just 7% in 2018 from 25% in 2005. Phase 4 are post marketing studies and the share has reduced from 16% in 2005 to 7% in 2018.

4. Study Submission Trend by DMC-
The DMC flag tells if the study has a Data Monitoring Committee appointed or not. There were many studies that did not mention if they have DMC or not. As I mentioned in the beginning, the chart is the representation of only studies that has the data and others were filtered out.
The share of DMC appointed studies increased in the first few years and then start to drop until 2008 after which it picked up again a bit and maintaining the 40% level until 2013 but falling down a bit to 34% in 2018.
Feel free to share your thoughts.
See you soon in the next post.
  

Clinical Intelligence Analytics - Growth Trends

Trial Growth Trends Dashboard

Growth Trends Dashboard provides insights into the growth trends of clinical trials over a period of time. This helps us gauge how the industry is growing. 

Below (Figure 2.1) is a snapshot of the dashboard without any data filters. Figure 2.2 is another representation to view the Year over Year growth. Year 2019 is the current year and hence the decline should not be viewed as negative growth. We still have few months remaining in 2019.

Figure 2.1

Figure 2.2

The Dashboard has the same summary tiles on top of the dashboard except a new metric to measure average number of days from registration to study initiation or enrollment. The average for prospectively registered studies is 107 days, which means that it takes 107 days on an average for a study to enroll its first patient after it has been registered.

Broadly, there are 4 times that are important milestones from study registration to the posting of results. The trends in this dashboard shows these 4 important milestones. The Growth Trends Dashboard can answer some of the following questions:
1. How the study registration in the US has grown over the last 20 years?
Registering the study is the first step and hence, it helps us in understanding how the industry is growing. A decline in study registration would mean less successful drugs or devices reaching the market. With patented drugs losing patent protection, a declining product pipeline can negatively impact the growth of the industry. CRO(Clinical Research Organisations) conduct the clinical trials on behalf of the sponsors and hence a decline in study registration can put brakes on the growth of CRO industry.
The study registration trend is increasing consistently except in year 2005 and 2008 that saw a sudden jump. International Committee of Medical journal Editors(ICMJE) began requiring trial registration as a condition of publication in September 2005. This explains the jump in 2005. The jump in year 2008 could be related to the recession period.
Beyond 2008, there has been consistent growth sometimes in double digits. The outlook for the industry as a whole looks positive.

2. Has the growth in the studies initiated been consistent?
Sponsors take lot's of efforts in initiating a study. It's a commitment they make in terms of money and efforts and hence it is an important indicator to see the growth in study initiation. The average duration for a study to go from registration to initiation is 326 days.
The growth in number of studies initiated over the last 20 years is also consistent until 2016. The growth has declined in last 2 years around -6.5% YOY. Year 2019 may also end up following the declining trend. The rate of YOY growth has consistently gone down from 42% in 2002 to -6.5% in 2018. If the trend continues, the coming years may prove to be difficult for the industry and companies need to start looking at alternatives to increase the product pipeline.
3. Are studies being completed growing consistently?
Completing the study is like clearing a big hurdle in drug development. Conducting a study is lengthy, costly, complex and risky and hence a successful completion is a big milestone and a big relief to sponsors.
The growth in studies completed over the last 20 years has been positive and consistent until last year 2018 when the growth was negative. The rate of growth declined consistently after 2007 with a recovery in 2014. The rate of growth came down to 1% in 2017 and then dropped to -8.5% in 2018. The current year 2019 doesn't look to be making any recovery. With just few months remaining, 2019 is 64% away from last year 2018. 
4. Are sponsors submitting study results growing?
ClinicalTrials.gov launched the results database in September 2008 and hence sponsors started posting the results after that. 
The trend shows that the posted results increased at a very high rate until 2014 recovering 39% in 2017 but again declined 20% in 2018. Current year 2019 seems to be matching up but it is yet to be seen if it will end with a positive growth.
If you notice, I compared the current year 2019 with last year 2018 to get an understanding of the current year performance. I did get some fair idea but I wanted to go one level down and see the current year has performed on a quarterly and monthly basis as compared to the last year. I wanted to see if there is any trend where there is high activity in certain months, so I created a dashboard which can provide some insights into understanding the current year performance in Figure 2.3.

Figure 2.3

The four tabular reports on the top row compares the monthly comparisons of current year months with previous year months. The increase column is the difference and appear in green or red based on whether the change is positive or negative. The bar charts on the bottom row compares the same metrics on quarter basis. Remember, August is the current month and hence the third quarter will not have complete values.
Let's take a look at all 4 metrics one by one and make some observations.
1. Study Submissions:
Current year has performed well so far and the number of studies have maintained a positive growth when compared with the same period of last year. Observe that last August had the highest number of studies submitted and unless there is a trend to submit the studies in the last few days of the month, we can expect August to play fairly well but may not be able to exceed. The lead current year has maintained in the first 2 quarters may help to gain a positive growth this year in number of studies submitted.
2. Studies Initiated:
So far, not a single month with a positive growth and the current year months have unperformed with a large margin. There are no months in the remaining period with unusually high or low activity and so if the trend continued, we may see a large drop in the 2019 study initiations as compared to 2018. I will keep an eye on that in the coming months and share with the readers here.
3. Studies Completed:
The monthly and quarterly numbers looks disappointing similar to study initiation. December month has high numbers possibly due to year end activities so we can expect some improvement in filling in the gap but the overall outlook doesn't look promising. 2019 may end up with a significant drop as compared to 2018.
4. Study postings:
The first two quarters have performed well and the current quarter also looking good. Hopefully, 2019 would see some positive growth. 
With that positive note, see you till next time. 

Clinical Intelligence Analytics - Summary

Clinical Summary Dashboard

Summary Dashboard gives an overall picture of clinical trials in a summarized form at a high level. 

Below (Figure 1.1) is a picture of the dashboard without any data filters. If I make any selection or filter, I will call it out and mention it.

Figure 1.1

The Dashboard tries to answer some basic questions to start with, and then we start looking at things from different angles and dimensions. 

The summary Dashboard can answer some of the following questions:

1. How many studies have been registered so far in the US?

This the total number of studies registered in the database. As on 09-Aug-2019, there are 313,345 studies registered in the US.

2. How many studies did actually started?

A study is considered to be started when it enrolls its first patient. It's an important milestone in the entire clinical trial process. 291,364 out of 313,345 which is around 93% of the studies did actually start by enrolling a patient.

3. How many studies did actually completed? 

Another important milestone is when a study completes and the patients who participated in the study stops receiving the drug. Of the 291,364 studies that started, 167,511 studies were completed, which is 58%. 

4. For how many studies did the sponsors posted the results?

Once the study is completed, the data collected is analyzed and the results are posted. Results Database was initiated in 2008 whereas the study registration began in 2000, so there might be studies without posted results. 38,127 studies have results posted out of 167,511 completed studies which is 23%.    

5. How many studies are currently recruiting patients?

A study recruits patients as study facility location called study sites. These study locations could be in many countries. 54,968 studies are presently enrolling patients including the ones that are enrolling only by invitation. This means 19% studies of the 291,365 studies that were started are still recruiting patients. 

6. How many patients were recruited in the past?

There were few enrollment values such as 99999999 that were converted to 0. About 490 Million people participated in the clinical trials across the globe from 210 countries. As per the recent United Nations estimate, the would population is 7.7 billion. We can say that 6.4% of world population has participated in clinical trials of the US. Other countries may have their own clinical trials registry.

7. What is the average duration of study completion?

Duration is the difference in the start and completion date of the study. 2.62 years is the average duration for a study to complete. Phase 3 trials are large scale studies and takes longer than phase 1 and 2, but we will look at that later. We can say that it will take around 8 years for a new drug to complete all the phases of clinical trials before it can apply to FDA for approval. Add another year or 2 for pre-clinical testing of the drug on laboratory animals. Now I understand how lengthy, complex and risky is the entire process of drug development. I will not go into the drug pricing strategies but you got a sense why those drugs are so un-affordable, even with insurance sometimes.

8. How many total sponsors registered the studies?

28,068 sponsors from both industry and non-industry (government agencies etc) have registered studies. We will see the ratio and proportions later.

9. What share of registered studies were interventional or observational?

Almost 80% of the studies are interventional studies where some kind of therapy is given to the participant.

10. What percentage of registered studies were sponsored by industry and non-industry sponsor?

Non-Industry sponsors leads with 3/4th of studies sponsored by them.

11. Top 10 sponsors who registered the most studies?

GSK is the leader. Pfizer and Astrazeneca are other sponsors from pharmaceutical industry following with a close margin. National Cancer Institute, a non-industry sponsor, is at a second position. 

12. What are the top medical conditions for which the studies were registered?

Surprised to see obesity at number 2. Asthma and depression are in top 10. I never thought they were so important but I guess our lifestyle changes are responsible for their growth. Breast cancer is the most studied medical condition.

13. What is percentage share by the overall status of the study?

Only a small portion of the studies were withdrawn and suspended, however, 5.65% studies were terminated which could be a cause of concern.

14. What are the top 10 countries that recruited the patients?

US has recruited about 18% of the total participants. 

Taiwan at no 2 surprised me. I found it enrolled around 67 million participants for an observational study but Taiwan's total population is around 25 million. The enrollment number is an outlier to me, however, I did not change it. Cambodia too has a study that enrolled 15 million participants for an observational patient registry sponsored by non-industry sponsor French National Institute. 

Since observational studies enroll large population of participants, let's look at who are the top countries who recruited for interventional studies only (Figure 1.2). Almost 82 million participants have been enrolled so far and US once again leads the chart with a contribution of little over 13% and China closing the gap at second position.   

Figure 1.2

You can always slice and dice the analysis to look at things from different perspective in a dashboard. It's real fun to create your own questions in your mind and then try to find out the answers yourself.

See you till next time.

Clinical Intelligence Analytics - Insights

Clinical Trial studies a new drug or device before it is brought to the market. The new therapy is tested on human subjects to evaluate its safety and efficacy.
Sponsors or investigators of certain clinical trials are required by U.S. law to register their trials on and submit summary results to ClinicalTrials.gov website. 
While working for a CRO as a Business Intelligence and Data warehouse Engineer, I gained some basic knowledge about the Clinical Research. I got so much interested that I decided to study Bio-sciences Management and Analytics subjects in my graduate MBA program. Unfortunately, my curiosity and the desire to learn more about Bio-sciences did not end there. 
I am passionate about creating insights out of data and I always try to unravel the layers of my curiosity by diving deep into the data. So, I decided to get the data from ClinicalTrials.gov and create Clinical Intelligence Analytics for myself. Here is the link in case you want to download it too.: https://aact.ctti-clinicaltrials.org/
The objective of creating this application is to share the insights with the community so that they know more about the things happening in this space. I would be really happy if this application could be of any benefit to patients, physicians,sponsors and other partners of the ecosystem. There are few online websites that helps patients find the recruiting study. However, I did not find any easy way that can help patients find out more about particular studies or sponsors or investigators in the past so that they can make informed decisions.
I used Talend software to get the data and used Qlikview BI to do data preparation and to create analytic dashboards. I have created more than a dozen dashboards so far and creating more as we go along. 
I would appreciate to leave a comment if you read the posts and find it useful. 
Since I do not want to make the posts boring for readers by putting a lot of information in one single post, I would be posting multiple posts in a series in coming days and update the link below in this post.

1. Clinical Summary Dashboard
2. Growth Trends Dashboard

Here are few links that would help in understanding basic terminology and basic information on ClinicalTrials.gov:
Common Terms
Trends Charts